1. Field of the Invention
The present invention relates to an association of plant proteins and plant polar lipids, preferably to an association of cereal proteins and cereal polar lipids and more preferably to an association of wheat prolamines and wheat polar lipids, for use in the delivery of active substances, including therapeutic and cosmetic agents, to humans.
2. Description of the Prior Art
Carrier systems for a variety of active substances including drugs, hormones, peptides, glycopeptides, growth factors and the like are well recognized in the art to be made of synthetic polymers.
Such systems particularly employed for delivering active agents to the skin for protection and renewal, or to the wound for healing and hemostasis, or further in the form of a device for dermal, transdermal, mucosal and transmucosal administration, should satisfy requirements such as:
to be non-toxic,
to not interrupt the delivery of an active substance to the application site and
to not interfere with the rate of release of the active substance,
to not cause irritation,
to be removed easily without discomfort, when needed,
to not deteriorate, peel or loosen over the period of application, and
moreover, to not leave a residue upon removal, when especially applied onto the skin.
Natural polymers, namely collagen and gelatin, have also been used as encapsulating agents, carriers, supporting agents, dispensers, etc., for delivering active agents.
Collagen, a biodegradable polymer found in man, has been used for the preparation of a patch employed in visceral surgery as disclosed in U.S. Pat. No. 5,201,745, the preparation of a pad for promoting hemostasis, treating traumatized tissues or expediting tissue suture as taught in WO-A-93/10731.
Similarly, collagen membranes have been used for delivering active substances as disclosed in EP-A-0 621 044, while collagen films were proposed to improve controlled drug delivery as described in WO-A-95/28964 and EP-A-0 518 697.
Chitin, another biopolymer abundant in crustaceans, has been proposed for achieving hemostasis as disclosed in U.S. Pat. No. 4,394,373 and for the preparation of corneal bandages and contact lenses in EP-A-0 486 294. Chitin and chitosan, its deacetylated product, have been proposed for the preparation of sustained release formulations as described in EP-A-0 187 703.
In general, polymers of natural origin as those given above, can not be considered as lacking any undesirable effect, especially those associated with an induction of an immune response. For instance, the antigenicity of collagen mainly depends on the animal species, so that there is always a need of sophisticated processing methods which could yield a least antigenic collagen. Similarly, products of marine shells are also implicated in inducing allergy to humans. Furthermore, recent evidence relates the transmission of diseases primarily originated in animal species to the humans after using/consuming animal products.
Therefore, there is a need for a natural polymer, pure and safe depriving any antigenic property, which can further be employed as a carrier system for active compounds.
The present invention uses such a natural polymer in the form of a new association of proteins and polar lipids all of plant origin, preferably an assocation of cereal proteins and plant polar lipids and more preferably an assocation of prolamines and cereal polar lipids.
Furthermore, the invention relates to the use of such an association as a carrier system in the form of a film or a patch for dermal (topical), transdermal, mucosal, transmucosal application, and also for skin healing and protection, wound healing and hemostasis.
The invention also refers to a carrier system in the form of a film or a patch further comprising active compounds and other additives which optimize the system""s properties.
The invention mainly refers to the use of a natural polymer, preferably made of a prolamine protein from corn or wheat, i.e. zein or gliadin, respectively. In the present invention, gliadin is preferred but no limitation in using other prolamines or a mixture thereof is considered.
The invention also refers to the use of polar lipids of plant origin, preferably to the use of plant ceramides or polar lipid compositions rich in plant ceramides. In the present invention, plant ceramides and in particular cereal ceramides (glycosylated or not, or a mixture thereof) are preferred but no limitation in using other plant lipids or a mixture thereof is considered.
The invention also refers to the use of a particular gliadin fraction, selected as to optimize the physicochemical properties of the said polymer and further to improve its efficacy as a carrier system.
The invention preferably refers to a new gliadin-plant ceramides association used as a carrier system for the delivery of active substances to humans by dermal, transdermal, mucosal and transmucosal administration and also as a carrier system for skin protection and healing, wound healing and hemostasis.
The term xe2x80x9cactive substancesxe2x80x9d as used herein includes any therapeutic or cosmetic agent.
Furthermore, the term xe2x80x9ctherapeutic agentxe2x80x9d as used herein includes any inorganic or organic compound without limitation, with both hydrophilic and hydrophobic properties, known in the art to be used for the treatment of certain disorders.
Moreover, the term xe2x80x9ccosmetic agentxe2x80x9d as used herein, includes any compound known in the art to be used for improving skin appearance.
The invention still refers to a carrier system in the form of a film or a patch adapted/adjusted in multi-shape and -size suitable for its application onto a selected site. The term xe2x80x9cselected sitexe2x80x9d as used herein, means any part of the skin or mucosa.
The invention yet refers to a prolamine-plant polar lipid association, more particularly to a gliadin-cereal ceramide association in the form of a film or a patch used as a drug carrier system, capable of administering the active substances systemically or topically.
The terms xe2x80x9csystemicallyxe2x80x9d and xe2x80x9ctopicallyxe2x80x9d as used herein, mean that the active substances will reach or not the systemic circulation, respectively.
The invention yet still refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association, particularly in the form of a patch, for direct application onto the skin.
The invention yet further refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association, particularly in the form of a patch wherein the said association is sandwiched between a backing film and a removable layer.
The invention yet further refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association, particularly in the form of a film, the formation of which being achieved in situ onto the skin or by an appropriate processing.
The invention yet also refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association in the form of a film or a patch used as a drug carrier system applied, without limitation to those applications, for transdermal delivery of drugs, or delivery of cosmetically active agents, or delivery of topically active agents such as those for treating dermal and nail diseases and pain relievers such as for treating arthritis, or delivery of buccally active agents such as those applied for pre- and post-dental operations, dental hygiene and for systemic treatment of various diseases through the mouth mucosa, or delivery of active agents through vaginal, nasal and ocular mucosa.
The invention yet still refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association in the form of a film or a patch used as a drug carrier system applied, without limitation, for the delivery of drugs for skin protection and healing, wound healing and hemostasis.
The invention also refers to a prolamine-cereal polar lipid association, more particularly to a gliadin-cereal ceramide association in the form of a film or a patch for topical or transdermal drug delivery, which is easily produced and is stable for a desirable time length and safe to be worn by humans.
The term xe2x80x9cstablexe2x80x9d as used herein, means that, during storage, any chemical changes that may occur will not affect its therapeutic efficacy before the expiration of a predetermined time.
The term xe2x80x9csafexe2x80x9d as used herein, means that no undesirable effects are induced upon its application to humans.